RESUMEN
ABSTRACT: In newly diagnosed transplant-ineligible patients with myeloma, daratumumab has improved outcomes when added to the standard-of-care regimens. In a randomized trial, we tested whether similar improvements would be observed when daratumumab was added to the bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen. Transplant-ineligible patients with untreated myeloma were randomized to receive VCD or VCD plus daratumumab (VCDD). A total of 121 patients were randomized: 57 in the VCD arm and 64 in the VCDD arm. Baseline characteristics were balanced between the 2 arms. The median progression-free survival (PFS) was 16.8 months (95% confidence interval [CI], 15.3-21.7) and 25.8 months (95% CI, 19.9-33.5) in the VCD and VCDD arms, respectively (hazard ratio, 0.67; log-rank test P = .066). In a preplanned analysis, it was demonstrated that the daratumumab-containing arm showed a significant improvement in PFS from 18 months onward, based on estimates at fixed time points after randomization. The proportions of patients who were progression-free at the following time points were: 18 months, 48% vs 68% (P = .0002); 24 months, 36% vs 52% (P = .0001); and 30 months, 27% vs 41% (P < .0001) in the VCD and VCDD arms, respectively. The best overall response and very good partial response rate were significantly higher in the daratumumab arm compared with the VCD and VCDD arms, respectively (65% vs 86%, P = .007; and 28% vs 52%, P = .009). Seventy-two percent of the VCDD patients completed the 9 cycles of induction therapy with no grade 3 or 4 peripheral neuropathy adverse events. This study supports VCDD as an option for the initial treatment of transplant-ineligible patients with myeloma. This trial was registered at the Australian New Zealand Clinical Trials Registry (ACTRN12617000202369).
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Anticuerpos Monoclonales , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Ciclofosfamida , Dexametasona , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Anciano , Masculino , Persona de Mediana Edad , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
BACKGROUND: Few Australasian autologous stem cell transplantation (ASCT) programmes perform ASCT in the private sector. Relatively little is known about ASCT outcomes in the private sector, which varies in care delivery models to the public system. AIMS: To investigate transplantation activity and survival outcomes at Icon Cancer Centre's Brisbane-based private clinical and laboratory ASCT programme over a 23-year period. METHODS: Retrospective, observational study of all adults who underwent ASCT at Icon between 1996 and 2018. Main outcome measures were transplant activity, overall survival (OS) and 100-day and 1-year transplant-related mortality (TRM). Outcomes were benchmarked against the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). RESULTS: Between 1996 and 2018, 1676 ASCT were performed in 1454 patients. From 2010 to 2018, ASCT performed at Icon contributed 40% of all South East Queensland ASCT. In the past 5 years, 21% of Icon's patients were aged ≥70 years, compared with 5% across Australasia. For the entire cohort, 100-day and 1-year TRM was 1.1% and 1.7%, respectively, while for those aged ≥70 years, it was 2.0% and 3.1%. For ASCT performed between 2014 and 2018, 100-day and 1-year TRM was 0.8% and 1.4%, which was half the TRM rates reported by the ABMTRR. The 10-year post-transplant OS at Icon was higher than the ABMTRR data, across all disease subtypes. CONCLUSION: We report excellent OS and low TRM, demonstrating the critical role of the private sector in the administration of this highly complex therapy. The Icon ASCT programme is the largest ASCT contributor in Queensland. It is inclusive of patients aged ≥70 years, demonstrating low and acceptable TRM.
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Trasplante de Células Madre Hematopoyéticas , Adulto , Humanos , Estudios Retrospectivos , Trasplante Autólogo , Sector Privado , Supervivencia sin Enfermedad , Trasplante de Células MadreRESUMEN
In central Australia, an area that is endemic for the human T-cell leukaemia virus type-1 (HTLV-1), the prevalence of Strongyloides stercoralis and its association with other health conditions are unknown. A cross-sectional community-based survey was conducted in seven remote Aboriginal communities in central Australia, from 2014 to 2018. All residents aged ≥10 years were invited to complete a health survey and to provide blood for Strongyloides serology, HTLV-1 serology and HTLV-1 proviral load (PVL). Risk factors for Strongyloides seropositivity and associations with specific health conditions including diabetes and HTLV-1 were determined using logistic regression. Overall Strongyloides seroprevalence was 27% (156/576) (children, 22% (9/40); adults (≥15 years), 27% (147/536), varied widely between communities (5-42%) and was not associated with an increased risk of gastrointestinal, respiratory or dermatological symptoms. Increasing age, lower HTLV-1 PVL (<1000 copies per 105 peripheral blood leucocytes) compared to the HTLV-1 uninfected group and community of residence were significant risk factors for Strongyloides seropositivity in an adjusted model. A modest reduction in the odds of diabetes among Strongyloides seropositive participants was found (aOR 0.58, 95% CI 0.35, 1.00; p = 0.049); however, this was lost when body mass index was included in the adjusted model (aOR 0.48, 95% CI 0.48, 1.47; p = 0.542). Strongyloides seropositivity had no relationship with anaemia. Exploring social and environmental practices in communities with low Strongyloides seroprevalence may provide useful lessons for similar settings.
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Diabetes Mellitus , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Strongyloides stercoralis , Estrongiloidiasis , Adulto , Animales , Australia/epidemiología , Niño , Estudios Transversales , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/epidemiología , Humanos , Leucemia de Células T/complicaciones , Estudios Seroepidemiológicos , Estrongiloidiasis/diagnóstico , Estrongiloidiasis/epidemiologíaRESUMEN
Infection with the human T cell leukaemia virus type 1 (HTLV-1) subtype C is endemic among Aboriginal people in central Australia. To provide insights into the risk factors for transmission, we conducted the first large-scale, community-based prevalence study in seven remote Aboriginal communities. Residents >2 years old were invited to participate in the study between August 2014 and June 2018. HTLV-1 infection was defined as a positive western blot (WB) test or a positive HTLV-1 PCR. 720 community residents participated in the study (children <15 years, 142; adults, 578). Prevalences for children and adults were 3.5% (5/142) and 36.8% (213/578), respectively, reaching 49.3% (106/215) for those older than 45 years. A wide range of proviral loads were measured for both asymptomatic and symptomatic participants with no difference within groups according to age or gender; however, median PVL was 1.34 log10 higher for symptomatic participants. The adult prevalence of HTLV-1 infection in central Australia is the highest reported worldwide. Sexual contact is likely to be the predominant mode of transmission.
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Infecciones por HTLV-I/epidemiología , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Adolescente , Adulto , Anciano , Australia/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Infecciones por HTLV-I/transmisión , Virus Linfotrópico T Tipo 1 Humano/clasificación , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Linfoma de Células T/epidemiología , Linfoma de Células T/virología , Masculino , Persona de Mediana Edad , Prevalencia , Provirus/genética , Provirus/aislamiento & purificación , Factores de Riesgo , Encuestas y Cuestionarios , Carga Viral , Adulto JovenAsunto(s)
Hematología , Hepatitis B , Hepatitis B/tratamiento farmacológico , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B , Antígenos del Núcleo de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Humanos , Inmunoglobulina M , Inmunoglobulinas IntravenosasRESUMEN
The primary analysis of the phase 3 ALCANZA trial showed significantly improved objective responses lasting ≥4 months (ORR4; primary endpoint) and progression-free survival (PFS) with brentuximab vedotin vs physician's choice (methotrexate or bexarotene) in CD30-expressing mycosis fungoides (MF) or primary cutaneous anaplastic large-cell lymphoma (C-ALCL). Cutaneous T-cell lymphomas often cause pruritus and pain; brentuximab vedotin improved skin symptom burden with no negative effects on quality of life. We report final data from ALCANZA (median follow-up, 45.9 months). Adults with previously treated CD30-expressing MF/C-ALCL were randomly assigned to brentuximab vedotin (n = 64) or physician's choice (n = 64). Final data demonstrated improved responses per independent review facility with brentuximab vedotin vs physician's choice: ORR4; 54.7% vs 12.5% (P < .001); complete response, 17.2% vs 1.6% (P = .002). Median PFS with brentuximab vedotin vs physician's choice was 16.7 months vs 3.5 months (P < .001). Median time to the next treatment was significantly longer with brentuximab vedotin than with physician's choice (14.2 vs 5.6 months; hazard ratio, 0.27; 95% confidence interval, 0.17-0.42; P < .001). Of 44 patients in the brentuximab vedotin arm who experienced any-grade peripheral neuropathy, (grade 3, n = 6; grade 4, n = 0), 86% (38 of 44) had complete resolution (26 of 44) or improvement to grades 1 and 2 (12 of 44). Peripheral neuropathy was ongoing in 18 patients (all grades 1-2). These final analyses confirm improved, clinically meaningful, durable responses and longer PFS with brentuximab vedotin vs physician's choice in CD30-expressing MF or C-ALCL. This trial was registered at https://www.clinicaltrials.gov as #NCT01578499.
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Linfoma Cutáneo de Células T , Médicos , Neoplasias Cutáneas , Adulto , Brentuximab Vedotina , Humanos , Linfoma Cutáneo de Células T/tratamiento farmacológico , Calidad de Vida , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
INTRODUCTION: Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, can lead to disfiguring lesions, debilitating pruritus and frequent skin infections. This study assessed response to brentuximab vedotin in patients with MF in the phase III ALCANZA study. METHODS: Baseline CD30 levels and large-cell transformation (LCT) status were centrally reviewed in patients with previously-treated CD30-positive MF using ≥2 skin biopsies obtained at screening; eligible patients required ≥1 biopsy with ≥10% CD30 expression. Patients were categorised as CD30min < 10% (≥1 biopsy with <10% CD30 expression), or CD30min ≥ 10% (all biopsies with ≥10% CD30 expression) and baseline LCT present or absent. Efficacy analyses were the proportion of patients with objective response lasting ≥4 months (ORR4) and progression-free survival (PFS). RESULTS: Clinical activity with brentuximab vedotin was observed across all CD30 expression levels in patients with ≥1 biopsy showing ≥10% CD30 expression. Superior ORR4 was observed with brentuximab vedotin versus physician's choice in patients: with CD30min < 10% (40.9% versus 9.5%), with CD30min ≥ 10% (57.1% versus 10.3%), with LCT (64.7% versus 17.6%) and without LCT (38.7% versus 6.5%). Brentuximab vedotin improved median PFS versus physician's choice in patients: with CD30min < 10% (16.7 versus 2.3 months), with CD30min ≥ 10% (15.5 versus 3.9 months), with LCT (15.5 versus 2.8 months) and without LCT (16.1 versus 3.5 months). Safety profiles were generally comparable across subgroups. CONCLUSION: These exploratory analyses demonstrated that brentuximab vedotin improved rates of ORR4 and PFS versus physician's choice in patients with CD30-positive MF and ≥1 biopsy showing ≥10% CD30 expression, regardless of LCT status. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01578499.
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Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Conducta de Elección , Técnicas de Apoyo para la Decisión , Antígeno Ki-1/metabolismo , Micosis Fungoide/tratamiento farmacológico , Médicos/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Agencias Internacionales , Masculino , Persona de Mediana Edad , Micosis Fungoide/metabolismo , Micosis Fungoide/patología , Médicos/psicología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
We report a case of progressive light-chain amyloidosis (otherwise known as AL amyloidosis) with acquired factor X (aFX) deficiency with a complete haematological response and rapid normalisation of FX levels following daratumumab monotherapy. To our knowledge, this is the first case report documenting successful treatment with daratumumab of aFX deficiency secondary to AL amyloidosis. The patient responded well to this therapy, with excellent symptomatic and quality of life improvements as well as a reduction in bleeding manifestations. This case highlights the value in considering daratumumab treatment when AL amyloidosis is complicated by FX deficiency.
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Amiloidosis , Deficiencia del Factor X , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Amiloidosis/tratamiento farmacológico , Deficiencia del Factor X/complicaciones , Deficiencia del Factor X/tratamiento farmacológico , Hemorragia , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Calidad de VidaRESUMEN
Recovery-oriented mental health practice guidelines recommend regular consumer involvement in care plans, yet in many acute settings, these are not routinely created thereby compromising accountability. This study explored the impact of workplace culture on the capacity of mental health nurses to involve consumers in care planning and consequently to work accountably. A focused ethnography was undertaken in one Australian inpatient unit involving mental health nurses and other health professionals. Data were derived from in-depth semistructured interviews with 12 nurses and 6 months of nonparticipant observation of multidisciplinary meetings and clinical handovers. Workplace culture had an impact on mental health nurses' accountability practices. A culture that prioritized reduction in length of stay resulted in less recovery-oriented care. Health professionals who paid more attention to crisis and risk management resulted in fewer opportunities for consumer-involved care planning.
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Trastornos Mentales/terapia , Enfermeras y Enfermeros/psicología , Cultura Organizacional , Planificación de Atención al Paciente , Participación del Paciente/psicología , Responsabilidad Social , Lugar de Trabajo/psicología , Antropología Cultural , Australia , Humanos , Salud Mental , Servicios de Salud Mental , Gestión de RiesgosRESUMEN
PURPOSE: This two-year (2016-2018) study aimed to identify what a good life is for Aboriginal people with disability in remote Central Australia and how service providers can support them to achieve a good life. This paper presents the findings that relate to barriers to delivering services for Aboriginal people with disability. METHODS: In-depth interviews and focus groups were held with Aboriginal people with disability and their carers aged at least 18 years from the Ngaanyatjarra Pitjantjatjara Yankunytjatjara (NPY) Lands and community organisations providing services there. The data were analysed using thematic analysis. RESULTS: There were 109 participants, of whom 47 were workers in service provider organisations and 62 were Aboriginal people. From the data, barriers to delivering services to support Aboriginal people to live a good life and solutions to overcome the barriers, were identified and described under the headings of environmental barriers and systemic issues. CONCLUSIONS: We discuss the policy implications of these findings with regard to addressing Indigenous disadvantage and how governments, service providers, communities, and Aboriginal people with disability and their families can work in partnership to address these barriers.Implications for RehabilitationIndigenous people with disability living in remote and very remote communities experience significant access and equity barriers to culturally responsive services that enable them to live a socially and culturally engaged life.Localised government and service provider disability policy approaches in Indigenous communities need to focus on both environmental and systemic issues.Greater investment in local remote communities is required to build the capacity of Indigenous families to support Aboriginal people with a disability to live a culturally and socially included life.
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Personas con Discapacidad , Servicios de Salud del Indígena , Adolescente , Adulto , Australia , Cuidadores , Humanos , Nativos de Hawái y Otras Islas del PacíficoRESUMEN
BACKGROUND: Circulatory diseases continue to be the greatest cause of mortality for Australian Aboriginal and Torres Strait Islander people, and a major cause of persistently lower life expectancy compared with non-Aboriginal Australians. The limited information that exists on atrial fibrillation (AF) prevalence in Aboriginal and Torres Strait Islander communities is mostly based on hospital admission data. This shows AF as principal or additional admission diagnosis was 1.4 times higher compared to non-Aboriginal Australians, a higher incidence of AF across the adult life span after age 20 years and a significantly higher prevalence among younger patients. Our study estimates the first national community prevalence and age distribution of AF (including paroxysmal) in Australian Aboriginal people. A handheld single-lead electrocardiograph (ECG) device (iECG), known to be acceptable in this population, was used to record participant ECGs. METHODS: This co-designed, descriptive cross-sectional study was conducted in partnership with 16 Aboriginal Community Controlled Health organisations at their facilities and/or with their services delivered elsewhere. The study was also conducted at one state community event. Three (3) Australian jurisdictions were involved: New South Wales, Western Australia and the Northern Territory. Study sites were located in remote, regional and urban areas. Opportunistic recruitment occurred between June 2016 and December 2017. People <45 years of age were excluded. RESULTS: Thirty (30) of 619 Aboriginal people received a 'Possible AF' and 81 an 'Unclassified' result from a hand-held smartphone ECG device. A final diagnosis of AF was made in 29 participants (4.7%; 95%CI 3.0-6.4%), 25 with known AF (five paroxysmal), and four with previously unknown AF. Three (3) of the four with unknown AF were aged between 55-64 years, consistent with a younger age of AF onset in Aboriginal people. Estimated AF prevalence increased with age and was higher in those aged >55 years than the general population (7.2% compared with 5.4%). Slightly more men than women were diagnosed with AF. CONCLUSIONS: This study is a significant contribution to the evidence which supports screening for AF in Aboriginal and Torres Strait Islander people commencing at a younger age than as recommended in the Australian guidelines (>65 years). We recommend the age of 55 years. Consideration should be given to the inclusion of AF screening in the Australian Government Department of Health annual 'Aboriginal and Torres Strait Islander Health Assessment'. CLINICAL TRIAL REGISTRATION: ACTRN12616000459426.
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Fibrilación Atrial/etnología , Electrocardiografía , Servicios de Salud del Indígena/organización & administración , Tamizaje Masivo/métodos , Nativos de Hawái y Otras Islas del Pacífico , Fibrilación Atrial/diagnóstico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nueva Gales del Sur/epidemiología , PrevalenciaRESUMEN
BACKGROUND: The human T-cell leukemia virus type 1 (HTLV-1) subtype c is endemic to central Australia. We report the first large-scale, community-based, health survey of HTLV-1 and its disease associations in this setting. METHODS: Aboriginal community residents aged >2 years in 7 remote communities were invited to do a health survey that included a questionnaire, spirometry, and clinical examination by a physician blinded to HTLV-1 status, clinical records, and spirometry results. Blood was drawn for HTLV-1 serology and proviral load (PVL). Pulmonary disease was assessed clinically and spirometrically and, where records were available, radiologically after the clinical assessment. Associations between specific diseases and HTLV-1 status were determined using logistic regression, adjusting for available confounders. RESULTS: Overall, 579 residents (164 children aged 3-17 years; 415 adults) were examined (37.7% of the estimated resident population). HTLV-1 prevalences for children and adults were 6.1% and 39.3%, respectively. No associations were found between HTLV-1 and any assessed clinical condition among children. Chronic pulmonary disease and gait abnormalities were more common among adults with HTLV-1 infection. Adjusted odds ratios among participants with PVL ≥1000 per 105 peripheral blood leukocytes were 7.08 (95% confidence interval [CI], 2.67-18.74; Pâ <â .001), 9.81 (95% CI, 3.52-27.35; Pâ <â .001), and 14.4 (95% CI, 4.99-41.69; Pâ <â .001) for clinically defined chronic pulmonary disease, moderate-severe expiratory airflow limitation, and radiologically determined bronchiectasis/bronchiolitis, respectively, and 5.21 (95% CI, 1.50-18.07; Pâ =â .009) for gait abnormalities. CONCLUSIONS: In the first study of HTLV-1 disease associations based on community recruitment and blinded assessment, HTLV-1 infection was strongly associated with pulmonary disease and gait abnormalities.
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Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Enfermedades Pulmonares , Estudios Transversales , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/epidemiología , Humanos , Carga ViralRESUMEN
It is mental health consumer's human right to lead a fulfilling life as they are empowered to actively manage their recovery. This can be facilitated through care planning, yet research suggests that the care plan is not routinely created, discussed, or updated in acute mental health settings. Research on care planning and the role of the mental health nurse highlights the importance of therapeutic communication in care plan development. This paper argues that the lack of meaningful care plan discussions between consumers and mental health nurses in an acute setting is a limitation to the practice of fully accountable mental health nursing care. We explore this limitation in quality care provision by examining literature on accountability and conclude that in mental health nursing, accountability is frequently enacted through an overarching focus on the organizational need to manage risks, rather than on therapeutic engagement.
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Planificación de Atención al Paciente , Participación del Paciente , Enfermería Psiquiátrica/métodos , Necesidades y Demandas de Servicios de Salud , Hospitales Psiquiátricos/organización & administración , Humanos , Trastornos Mentales/enfermería , Trastornos Mentales/psicología , Trastornos Mentales/terapia , Relaciones Enfermero-Paciente , Participación del Paciente/psicología , Gestión de RiesgosAsunto(s)
Errores Diagnósticos , Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Monitoreo Fisiológico , Análisis Mutacional de ADN , Reacciones Falso Negativas , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/normas , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidoresRESUMEN
OBJECTIVE: Examine the feasibility and acceptability of an electrocardiogram (ECG) attached to a mobile phone (iECG) screening device for atrial fibrillation (AF) in Aboriginal Controlled Community Health Services (ACCHS) and other community settings. METHODS: Semi-structured interviews were conducted with ACCHS staff in urban, rural and remote communities in three Australian states/territories. Quantitative and qualitative questions identified the enabling factors and barriers for staff and Aboriginal patients' receptiveness to the device. Mean quantitative scores and their standard deviation were calculated in Microsoft Excel and qualitative questions were thematically analysed. RESULTS: Eighteen interviews were conducted with 23 staff across 11 ACCHS. Quantitative data found staff were confident in providing iECG screening and managing the referral pathway, and thought the process was beneficial for patients. Qualitative data highlighted the usefulness of the device to undertake opportunistic screening and acceptability in routine practice, and provided opportunities to engage patients in education around AF. CONCLUSION: The iECG device was well accepted within ACCHSs and was feasible to use to screen for AF among Aboriginal patients. Implications for public health: The device can be used in clinical and community settings to screen Aboriginal people for atrial fibrillation to help reduce rates of stroke and other cardiovascular diseases.
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Fibrilación Atrial/diagnóstico , Teléfono Celular , Electrocardiografía/instrumentación , Tamizaje Masivo/métodos , Aplicaciones Móviles , Nativos de Hawái y Otras Islas del Pacífico , Aceptación de la Atención de Salud , Adulto , Australia , Electrocardiografía/métodos , Estudios de Factibilidad , Femenino , Humanos , Entrevistas como Asunto , Masculino , Atención Primaria de Salud , Investigación Cualitativa , Salud Rural , Población Rural , Población UrbanaRESUMEN
The management of CML in pregnancy is challenging with the need to balance disease control against potential teratogenic effects of TKI therapy. In this multi-center case-cohort study of 16 women in chronic phase, CML ceased TKI treatment pre- or post-conception during their first pregnancy. Thirteen patients were on imatinib; 9 ceased their TKI prior to conception and 7 ceased at pregnancy confirmation. Twelve patients had achieved either MMR or better at time of TKI cessation. Eleven women lost MMR during pregnancy and two patients lost CHR. Fourteen women reestablished MMR on TKI recommenced. The depth molecular response prior to conception appeared to correlate well with restoration of disease control on TKI recommencement though duration of MMR did not appear to be as important. While interruption of TKI treatment for pregnancy usually leads to loss of molecular response, loss of hematological response is uncommon and disease control is reestablished with resumption of therapy in the majority of women.
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Antivirales/uso terapéutico , Interferones/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/prevención & control , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Estudios de Casos y Controles , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Embarazo , Resultado del Embarazo , Resultado del Tratamiento , Adulto JovenRESUMEN
Standard treatment for higher risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low blast acute myeloid leukemia is azacitidine. In single arm studies, adding lenalidomide had been suggested to improve outcomes. The ALLG MDS4 phase II trial randomized such patients to standard azacitidine or combination azacitidine (75mg/m2/d days 1 to 5) with lenalidomide (10mg days 1-21 of 28-day cycle from cycle 3) to assess clinical benefit (alive without progressive disease) at 12 months. A total of 160 patients were enrolled; median age 70.7 years (range 42.5-87.2), 31.3% female with 14% chronic myelomonocytic leukemia, 12% acute myeloid leukemia and 74% myelodysplastic syndromes. Adverse events were similar in both arms. There was excellent delivery of protocol therapy (median azacitidine cycles 11 both arms) with few dose reductions, delays or early cessations. At median follow up 33.1 months (range 0.7-59.5), the rate of clinical benefit at 12 months was 65% azacitidine arm and 54% lenalidomide+azacitidine arm (P=0.2). There was no difference in clinical benefit between each arm according to WHO diagnostic subgroup or IPSS-R. Overall response rate was 57% in azacitidine arm and 69% in lenalidomide+azacitidine (P=0.14). There was no difference in progression- free or overall survival between the arms (each P>0.12). Although the combination of lenalidomide and azacitidine was tolerable, there was no improvement in clinical benefit, response rates or overall survival in higher risk myelodysplastic syndrome, chronic myelomonocytic leukemia or low blast acute myeloid leukemia patients compared to treatment with azacitidine alone. This trial was registered at www.anzc-tr.org.au as ACTRN12610000271000.
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Azacitidina/administración & dosificación , Crisis Blástica , Lenalidomida/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Anciano , Anciano de 80 o más Años , Azacitidina/efectos adversos , Crisis Blástica/tratamiento farmacológico , Crisis Blástica/mortalidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lenalidomida/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/mortalidad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
AIM: Idelalisib (IDELA) treatment is associated with diarrhea/colitis (incidence of â¼15% grade ≥3). We performed a retrospective analysis of gastrointestinal biopsies from 29 patients treated with IDELA across nine clinical trials. METHODS: A central core laboratory performed histopathologic review, immunohistochemistry, and droplet digital PCR viral studies. These results were correlated with tissue immune profiling data and morphologic features per modified Geboes score. RESULTS: Out of 29 eligible patients with abdominal pain or diarrhea, 24 (82.8%) had reported adverse event terms of diarrhea and/or colitis. Infectious pathogens were detected in 9/29 samples. Most biopsies presented with mixed/inflammatory infiltrates and contained increased numbers of FOXP3+ cells versus normal controls. CONCLUSION: This study revealed evidence of T-cell dysregulation and a substantial infectious component in association with IDELA-related diarrhea/colitis.
Asunto(s)
Colitis/inducido químicamente , Diarrea/inducido químicamente , Purinas/efectos adversos , Quinazolinonas/efectos adversos , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Biopsia , Colitis/tratamiento farmacológico , Colitis/patología , Colitis/virología , Colon/patología , Colon/virología , Infecciones por Citomegalovirus/patología , Diarrea/tratamiento farmacológico , Diarrea/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Recto/patología , Recto/virologíaRESUMEN
BACKGROUND: The Manning Cost-Benefit Tool (MCBT) was developed to assist criminal justice policymakers, policing organisations and crime prevention practitioners to assess the benefits of different interventions for reducing crime and to select those strategies that represent the greatest economic return on investment. DISCUSSION: A challenge with the MCBT and other cost-benefit tools is that users need to input, manually, a considerable amount of point-in-time data, a process that is time consuming, relies on subjective expert opinion, and introduces the potential for data-input error. In this paper, we present and discuss a conceptual model for a 'smart' MCBT that utilises machine learning techniques. SUMMARY: We argue that the Smart MCBT outlined in this paper will overcome the shortcomings of existing cost-benefit tools. It does this by reintegrating individual cost-benefit analysis (CBA) projects using a database system that securely stores and de-identifies project data, and redeploys it using a range of machine learning and data science techniques. In addition, the question of what works is respecified by the Smart MCBT tool as a data science pipeline, which serves to enhance CBA and reconfigure the policy making process in the paradigm of open data and data analytics.